title: Simultaneous quantitative analyses of indole and oxindole alkaloids of Uncaria Hook in rat plasma and brain after oral administration of the traditional Japanese medicine Yokukansan using high-performance liquid chromatography with tandem mass spectrometry.
abstract: Uncaria Hook (UH) alkaloids are involved in the beneficial effects of Yokukansan. However, the pharmacokinetics of UH alkaloids after oral administration of Yokukansan has not yet been sufficiently investigated. Therefore, we developed and validated a sensitive and specific high-performance liquid chromatography with tandem mass spectrometry (LC/MS/MS) method for the simultaneous quantitation of seven UH alkaloids (corynoxeine, isocorynoxeine, rhynchophylline, isorhynchophylline, hirsutine, hirsuteine and geissoschizine methyl ether) in rat plasma and brain. After protein precipitation with acetonitrile, chromatographic separation was performed using an Ascentis Express RP-amide column, with gradient elution with 0.2% formic acid and acetonitrile at 0.3 mL/min. All analytes in the plasma and brain showed good linearity over a wide concentration range (r > 0.995). Intra-day and inter-day variations of each constituent were 8.6 and 8.0% or less in the plasma, and 14.9 and 15.0% or less in the brain, respectively. The validated LC/MS/MS method was applied in the pharmacokinetic studies of UH alkaloids after oral administration of Yokukansan to rats. In the plasma, rhynchophylline, hirsutine, hirsuteine and geissoschizine methyl ether were detected, but only geissoschizine methyl ether was detected in the brain. These results suggest that geissoschizine methyl ether is an important constituent of the pharmacological effects of Yokukansan.
authors.affiliation: Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, 300-1192, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kushida
authors.forename: Miwako
authors.initials: M
authors.lastname: Fukutake
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tabuchi
authors.forename: Takao
authors.initials: T
authors.lastname: Katsuhara
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nishimura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ikarashi
authors.forename: Masanao
authors.initials: M
authors.lastname: Kanitani
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kase
mesh_terms: D000470:Alkaloids / Q000032:analysis / Q000097:blood / Q000737:chemistry*; D000818:Animals; D001923:Brain Chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D007211:Indoles / Q000032:analysis / Q000097:blood / Q000737:chemistry*; D016014:Linear Models; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods; D032070:Uncaria / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D004365:Drugs, Chinese Herbal; D007211:Indoles; C524644:Yi-Gan San
keywords: LC/MS/MS; Uncaria Hook alkaloid; Yokukansan; pharmacokinetics; rat